Generation and Exploitation of Aggregation Abstractions for Scheduling and Resource Allocation

Our research is investigating abstraction of computational theories for scheduling and resource allocation. These theories are represented in a variant of first order predicate calculus, parameterized multisorted logic, that facilitates specification of large problems. A particular problem is conceptually stated as a set of ground sentences that are consistent with a quantified theory. We are mainly investigating the automated generation of aggregation abstractions and approximations in which detailed resource allocation constraints are replaced by constraints between aggregate demand and capacity. We are also investigating the interaction of aggregation abstractions with the more thoroughly investigated abstractions of weakening operator preconditions. The purpose of the theories for aggregated demand/capacity is threefold: first, to answer queries about aggregate properties, such as gross feasibility; second, to reduce computational costs by using the solution of aggregate problems to guide the solution of detailed problems; and third, to facilitate reformulating theories to approximate problems for which there are efficient problem solving methods. We also describe novel methods for exploiting aggregation abstractions

Universal quantum computation and simulation using any entangling Hamiltonian and local unitaries

What interactions are sufficient to simulate arbitrary quantum dynamics in a composite quantum system? We provide an efficient algorithm to simulate any desired two-body Hamiltonian evolution using any fixed two-body entangling n-qubit Hamiltonian and local unitaries. It follows that universal quantum computation can be performed using any entangling interaction and local unitary operations.Comment: Added references to NMR refocusing and to earlier work by Leung et al and Jones and Knil

Equilibration of isolated macroscopic quantum systems

We investigate the equilibration of an isolated macroscopic quantum system in the sense that deviations from a steady state become unmeasurably small for the overwhelming majority of times within any sufficiently large time interval. The main requirements are that the initial state, possibly far from equilibrium, exhibits a macroscopic population of at most one energy level and that degeneracies of energy eigenvalues and of energy gaps (differences of energy eigenvalues) are not of exceedingly large multiplicities. Our approach closely follows and extends recent works by Short and Farrelly [2012 New J. Phys. 14 013063], in particular going beyond the realm of finite-dimensional systems and large effective dimensions.Comment: 19 page

Endogenous Transmembrane TNF-Alpha Protects Against Premature Senescence in Endothelial Colony Forming Cells

RATIONALE: Transmembrane tumor necrosis factor-α (tmTNF-α) is the prime ligand for TNF receptor 2, which has been shown to mediate angiogenic and blood vessel repair activities in mice. We have previously reported that the angiogenic potential of highly proliferative endothelial colony-forming cells (ECFCs) can be explained by the absence of senescent cells, which in mature endothelial cells occupy >30% of the population, and that exposure to a chronic inflammatory environment induced premature, telomere-independent senescence in ECFCs. OBJECTIVE: The goal of this study was to determine the role of tmTNF-α in the proliferation of ECFCs. METHODS AND RESULTS: Here, we show that tmTNF-α expression on ECFCs selects for higher proliferative potential and when removed from the cell surface promotes ECFC senescence. Moreover, the induction of premature senescence by chronic inflammatory conditions is blocked by inhibition of tmTNF-α cleavage. Indeed, the mechanism of chronic inflammation-induced premature senescence involves an abrogation of tmTNF/TNF receptor 2 signaling. This process is mediated by activation of the tmTNF cleavage metalloprotease TNF-α-converting enzyme via p38 MAP kinase activation and its concurrent export to the cell surface by means of increased iRhom2 expression. CONCLUSIONS: Thus, we conclude that tmTNF-α on the surface of highly proliferative ECFCs plays an important role in the regulation of their proliferative capacity

Characterization of Mott-insulating and superfluid phases in the one-dimensional Bose--Hubbard model

We use strong-coupling perturbation theory, the variational cluster approach (VCA), and the dynamical density-matrix renormalization group (DDMRG) method to investigate static and dynamical properties of the one-dimensional Bose--Hubbard model in both the Mott-insulating and superfluid phases. From the von Neumann entanglement entropy we determine the central charge and the transition points for the first two Mott lobes. Our DMRG results for the ground-state energy, momentum distribution function, boson correlation function decay, Mott gap, and single particle-spectral function are reproduced very well by the strong-coupling expansion to fifth order, and by VCA with clusters up to 12 sites as long as the ratio between the hopping amplitude and on-site repulsion, t/U, is smaller than 0.15 and 0.25, respectively. In addition, in the superfluid phase VCA captures well the ground-state energy and the sound velocity of the linear phonon modes. This comparison provides an authoritative estimate for the range of applicability of these methods. In strong-coupling theory for the Mott phase, the dynamical structure factor is obtained from the solution of an effective single-particle problem with an attractive potential. The resulting resonances show up as double-peak structure close to the Brillouin zone boundary. These high-energy features also appear in the superfluid phase which is characterized by a pronounced phonon mode at small momenta and energies, as predicted by Bogoliubov and field theory. In one dimension, there are no traces of an amplitude mode in the dynamical single-particle and two-particle correlation functions.Comment: 15 pages, 12 figure

Neurophysiology

Contains reports on seven research projects.National Institutes of Health (Grant 5 RO1 EY01149-02)Bell Telephone Laboratories, Inc. (Grant)National Institutes of Health (Grant 1 TO1 EY00090-01

Cognitive deficits in childhood, adolescence and adulthood in 22q11.2 deletion syndrome and association with psychopathology

22q11.2 Deletion Syndrome (22q11.2DS) is associated with high risk of psychiatric disorders and cognitive impairment. It remains unclear to what extent key cognitive skills are associated with psychopathology, and whether cognition is stable over time in 22q11.2DS. 236 children, adolescents and adults with 22q11.2DS and 106 typically developing controls were recruited from three sites across Europe. Measures of IQ, processing speed, sustained attention, spatial working memory and psychiatric assessments were completed. Cognitive performance in individuals was calculated relative to controls in different age groups (children (6–9 years), adolescents (10–17 years), adults (18+ years)). Individuals with 22q11.2DS exhibited cognitive impairment and higher rates of psychiatric disorders compared to typically developing controls. Presence of Autism Spectrum Disorder symptoms was associated with greater deficits in processing speed, sustained attention and working memory in adolescents but not children. Attention deficit hyperactivity disorder in children and adolescents and psychotic disorder in adulthood was associated with sustained attention impairment. Processing speed and working memory were more impaired in children and adults with 22q11.2DS respectively, whereas the deficit in sustained attention was present from childhood and remained static over developmental stages. Psychopathology was associated with cognitive profile of individuals with 22q11.2DS in an age-specific and domain-specific manner. Furthermore, magnitude of cognitive impairment differed by developmental stage in 22q11.2DS and the pattern differed by domain

Reverberations Exhibit

Interactive exhibit to correspond with the lectures given during the Reverberations series

TSG-6 is highly expressed in human abdominal aortic aneurysms

BACKGROUND: The formation of abdominal aortic aneurysms (AAA) is characterized by a dominance of proinflammatory forces that result in smooth muscle cell apoptosis, extracellular matrix degradation, and progressive diameter expansion. Additional defects in the antiinflammatory response may also play a role but have yet to be fully characterized. TSG-6 (TNF-stimulated gene-6) is a potent antiinflammatory protein involved in extracellular matrix stabilization and cell migration active in many pathological conditions. Here, we describe its role in AAA formation. METHODS: Blood and/or aortic tissue samples were collected from organ donors, subjects undergoing elective AAA screening, and open surgical AAA repair. Aortic specimens collected were preserved for IHC or immediately assayed after tissue homogenization. Protein concentrations in tissue and plasma were assayed by ELISA. All immune cell populations were assayed using FACS. In vitro, macrophage polarization from monocytes was performed with young, healthy donor PBMCs. RESULTS: TSG-6 was found to be abnormally elevated in both the plasma and aortic wall of patients with AAA compared with healthy and risk-factor matched non-AAA donors. We observed the highest tissue concentration of TSG-6 in the less-diseased proximal and distal shoulders compared with the central aspect of the aneurysm. IHC localized most TSG-6 to the tunica media with minor expression in the tunica adventitia of the aortic wall. Higher concentrations of both M1 and M2 macrophages where also observed, however M1/M2 ratios were unchanged from healthy controls. We observed no difference in M1/M2 ratios in the peripheral blood of risk-factor matched non-AAA and AAA patients. Interesting, TSG-6 inhibited the polarization of the antiinflammatory M2 phenotype in vitro. CONCLUSIONS: AAA formation results from an imbalance of inflammatory forces causing aortic wall infiltration of mononuclear cells leading to the vessel breakdown. In the AAA condition, we report an elevation of TSG-6 expression in both the aortic wall and the peripheral circulation

Metformin does not reduce inflammation in diabetics with abdominal aortic aneurysm or at high risk of abdominal aortic aneurysm formation

Introduction The protective effect of diabetes mellitus on abdominal aortic aneurysm formation and growth has been repeatedly observed in population studies but continues to be poorly understood. However, recent investigations have suggested that metformin, a staple antihyperglycemic medication, may be independently protective against abdominal aortic aneurysm formation and growth. Therefore, we describe the effect of metformin in abdominal aortic aneurysm and at-risk patients on markers of inflammation, the driver of early abdominal aortic aneurysm formation and growth. Methods Peripheral blood was collected from patients previously diagnosed with abdominal aortic aneurysm or presenting for their U.S. Preventive Task Force-recommended abdominal aortic aneurysm screening. Plasma and circulating peripheral blood mononuclear cells were isolated using Ficoll density centrifugation. Circulating plasma inflammatory and regulatory cytokines were assessed with enzyme-linked immunosorbent assays. CD4+ cell phenotyping was performed using flow cytometric analysis and expressed as a proportion of total CD4+ cells. To determine the circulating antibody to self-antigen response, a modified enzyme-linked immunosorbent assay was performed against antibodies to collagen type V and elastin fragments. Results Peripheral blood was isolated from 266 patients without diabetes mellitus (n=182), with diabetes mellitus not treated with metformin (n=34), and with diabetes mellitus actively taking metformin (n=50) from 2015 to 2017. We found no differences in the expression of Tr1, Th17, and Treg CD4+ fractions within diabetics ± metformin. When comparing inflammatory cytokines, we detected no differences in IL-1β, IL-6, IL-17, IL-23, IFN-γ, and TNF-α. Conversely, no differences were observed pertaining to the expression to regulatory cytokines IL-4, IL-10, IL-13, TSG-6, or TGF-β. Lastly, no differences in expression of collagen type V and elastin fragment antigen and/or antibodies were detected with metformin use in diabetics. Conclusion Metformin in diabetics at-risk for abdominal aortic aneurysm or diagnosed with abdominal aortic aneurysm does not seem to alter the peripheral inflammatory environment